Format

Send to

Choose Destination
Int J Cancer. 2016 Dec 15;139(12):2802-2811. doi: 10.1002/ijc.30402. Epub 2016 Sep 12.

TRAIL delivered by mesenchymal stromal/stem cells counteracts tumor development in orthotopic Ewing sarcoma models.

Author information

1
INSERM, UMR-957, Equipe labellisée LIGUE contre le CANCER 2012, Nantes, F-44035, France.
2
Université de Nantes, EA 3822, Faculté de Médecine, Laboratoire de Physiopathologie de la Résorption Osseuse et thérapie des tumeurs osseuses primitives, Nantes, F-44035, France.
3
Department of Medical and Surgical Sciences for Children and Adults, Laboratory of Cellular Therapy, University Hospital of Modena and Reggio Emilia, Modena, Italy.
4
INSERM, UMR-957, Equipe labellisée LIGUE contre le CANCER 2012, Nantes, F-44035, France. Francoise.Redini@univ-nantes.fr.
5
Université de Nantes, EA 3822, Faculté de Médecine, Laboratoire de Physiopathologie de la Résorption Osseuse et thérapie des tumeurs osseuses primitives, Nantes, F-44035, France. Francoise.Redini@univ-nantes.fr.

Abstract

Ewing sarcoma (EWS) is the second most frequent pediatric malignant bone tumor. EWS patients have not seen any major therapeutic progress in the last 30 years, in particular in the case of metastatic disease, which requires new therapeutic strategies. The pro-apoptotic cytokine TNF-Related Apoptosis Inducing Ligand (TRAIL) can selectively kill tumor cells while sparing normal cells, making it a promising therapeutic tool in several types of cancer. However, certain EWS cell lines appear resistant to recombinant human (rh) TRAIL-induced apoptosis. We therefore hypothesized that a TRAIL presentation at the surface of the carrier cells might overcome this resistance and trigger apoptosis. For this purpose, human adipose mesenchymal stromal/stem cells (MSC) transfected in a stable manner to express full-length human TRAIL were co-cultured with several human EWS cell lines, inducing apoptosis by cell-to-cell contact even in cell lines initially resistant to rhTRAIL or AMG655, an antibody agonist to the death receptor, DR5. In vivo, TRAIL delivered by MSCs was able to counteract tumor progression in two orthotopic models of Ewing sarcoma, associated with caspase activation, indicating that a cell-based delivery of a potent apoptosis-inducing factor could be relevant in EWS.

KEYWORDS:

Ewing sarcoma; MSC; TRAIL; microenvironment; resistance

PMID:
27558972
DOI:
10.1002/ijc.30402
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center